leanne (L3) Flashcards
cardiovascular disease CVD statistics
CVDs are the number one cause of death globally
~17.3 – 17.7 million people died from CVDs in 2008; 2015, representing 30 and 31% of all global deaths(WHO).
7.4 M CHD and 6.7 M S
Of these deaths, >66% from low- and middle-income countries
deaths predicted to increase to ~23.3. million by 2030
Most cardiovascular diseases can be prevented by addressing risk factors.
Protective oestrogen - lower risk of cardiovascular diseases
After menopause, you stop having the protective effect as much - same risk as males
types of CVDs
CVDs - A class of disorders affecting the heart, blood vessels (arteries, veins, capillaries) or both.
- Coronary heart disease (vasculature of the heart itself)
- Cerebrovascular disease (Occlusion of cerebral arteries of the brain and causes stroke)
- Hypertensive heart disease (Effect of high BP)
- Peripheral arterial disease ( Effect of peripheral vasculature - high complications if you have diabetes too)
- Rheumatic heart disease (Issue following the contraction of the rheumatic fever which affects the valves of the heart)
- Deep vein thrombosis and
pulmonary embolism. (Blood clots that move and get trapped in vasculature in the periphery and of the lungs)
Atherosclerosis
Atherosclerosis - precursor of all CVD
- The formation of atheroma – accumulation of lipid plaques within the walls of a vessel.
- Reduced arterial lumen
- Loss of perfusion
- Result of loss of elasticity – increases likeliness of rupture
- Predisposition to thrombus (clot) formation.
What is cardiovascular risk?
Epidemiological/statistical notion that can assist in assessing risk/benefit ratios for treatments, but is often used instead for rationing of limited health resources
For populations the overall risk of CVD events can be calculated with good predictive value by measuring various parameters and then employing ‘equations’ (derived from large cohorts in clinical trials or prospective epidemiological surveys- eg Framingham).
Frequently, assumed to be absolutely predictive in individuals!
measuring risk
risk calculators like frammingham score / QRisk scores / NICE
LDL :( high correlation with cardiovascular disease so has to be maintained < 3mmol/L
HDL :) good correlation with cardiovascular disease so has to be maintained > 1mmol/L
SOME HIGH RISK GROUPS
Age > 75 yrs, Family Hx of Premature CHD
Familial hypercholesterolaemia (FH)
Known Type2 Diabetes orCKD
Lipids and the Cardiovascular system
The insolubility of lipids requires a specific transport mechanism.
Carried out by LIPOPROTEINS (lipid protein complexes – individual proteins = APOLIPOPROTEINS - Cell surface receptors)
Chylomicrons, VLDL, IDL, LDL, HDL and Lipoprotein A.
Positive relationship between LDL-C and CVD
Inverse relationship with HDL –C and CVD
Classification of lipoproteins according to increasing density.
TABLE IN L3 S11
structure of lipoproteins
STRUCTURES IN L3 S12
exogenous lipid transport pathway
NOTES IN L3 S14
1 – VLDL synthesis, transport mainly TG to peripheral tissues.
2 – Loss of TG as a result of hydrolysis by LPL, leaves VLDL remnants or IDL.
3 – Formation of IDL and LDL, more TG are given up – LDL.
4 – LDL uptake via receptor-mediated endocytosis releasing cholesterol into the cells
Reverse cholesterol transport (HDL)
NOTES IN L3 S17
1 – HDL synthesis by liver and intestines
2 – Can interact with peripheral tissue cells (ABC-A1) and other lipoproteins to pick up unesterified C – esterification of C (LCAT)
3 – Some is transported to steroidogenic tissues.
4 – C Removal by receptor mediated endocytosis in the liver.
5 – And via LDL pathway.
6 – Acts as a store of apoproteins
Atherosclerosis - Pathogenesis
Generally affects medium to large arteries.
Characterised by:
- lipid deposition in the intima - smooth muscle and ECM proliferation - production of a protruding fibrous plaque
Can be asymptomatic until :
- Vessel lumen is sufficiently narrowed – Ischaemia - Sudden occlusion by plaque rupture and thrombosis - (MI) - Walls are weakened – Aneurysm. - Blood clot breaks lose - Embolism
Mechanisms underlying Atherosclerosis
DIAGRAMS OF MECHANISMS L3 S20-23
‘Lipid hypothesis’ – increased plasma lipid namely cholesterol, leads to CVD.
‘Response to injury hypothesis’- endothelial cell dysfunction
‘Inflammation hypothesis’ – most recent and ties the two together.
Neoplasia – abnormal proliferation of smooth muscle cells.
Prostaglandins – prostacyclin and thromboxane imbalance (can influence thrombus formation)
Thrombosis – the main event forming atheromatous plaques
Vulnerable plaques
In the coronary arteries, behaviour of plaque is determined not primarily by its size, but by composition.
Plaques with large lipid cores, thin fibrous caps and inflammatory cell infiltrates are more likely to rupture, exposing thrombogenic material of the plaque core and precipitating acute coronary events.
Only a small percentage occlude the lumen!
Drugs and clinical trials
Lifestyle changes – Obesity/smoking.
Targeting hypertension – (ACE inhibitors)
High Cholesterol – Statins
Thrombus formation – Antiplatelets (low-dose asprin, Clopidogrel.
Surgery - Coronary arteries (MI) Carotid arteries (Stroke)
Statins
HMG-CoA reductase inhibitors - limit the synthesis of Mevalonate.
Significantly reduces the synthesis of cholesterol in hepatocytes.
Increases cellular LDLR and so increases the clearance of LDL from the circulation.
Inhibit the synthesisi of Apo B-100
Atorvastatin – commonly prescribed.
